DESCRIPTION Tuberculosis (TB) is one of the major infectious diseases in the world and the development of an effective vaccine is a high priority, particularly for those infected with HIV-1. The applicant's phase I safety trial for a short term culture filtrate/adjuvant (STCF/A) vaccine has been under development for over two years and has been released from clinical hold by the FDA. Vaccine development requires greater understanding of the immune response in the lung. Specific Aim 1 will evaluate the immune response in patients with active pulmonary tuberculosis including patients co-infected with HIV-1 at baseline and six months after beginning therapy. He will compare their response to PPD+ and PPD- healthy individuals. He will evaluate their clinical status and study their BAL cells and peripheral blood mononuclear cells (PBMCs) by immunophenotyping of lymphocyte subsets and by proliferation, IFN-gamma release, and CTL assays to assess their in vitro response to STCF and PPD. Specific Aim 2 will be a phase I safety trial of STCF/A in PPD- normal volunteers. He will vaccinate at 10 mcg STCF/A, then escalate STCF/A doses to 50 mcg and 250 mcg and use multiple doses after demonstration of safety. He will determine if there is a DTH response, and whether the in vitro immune response of PBMCs to STCF correlate with DTH. Specific Aim 3 will be a phase II safety/immunogenicity trial of STCF/A in HIV-1 infected patients on antiretroviral therapy with CD4+ count equal to or greater than 200 to determine if intradermal STCF/A at the highest dose determined to be safe has an immunizing effect as measured by new in vitro responses specific for M. tb. proteins in PBMCs and BAL. This proposal will provide critical information on memory immunity in the lung when humans are infected/exposed to M. tb. and how this "protective" immune response to TB may be perturbated in AIDS.